ABSTRACT The transformative effect of Next Generation DNA sequencing (NGS) technologies on the biological and medical research community has resulted in an unprecedented potential for key discoveries at an accelerated pace not previously possible. The next generation instruments, such as the Illumina Genome Analyzer IIx (GAIIx), have led to creative experimental applications not possible with conventional capillary sequencing technology. We are requesting funding for a GAIIx to be operated as a multi-institutional shared resource for the University at Buffalo Center of Excellence for Bioinformatics and Life Sciences (UB-CoEBLS) and Roswell Park Cancer Institute (RPCI). The instrument will be located in the Infectious Disease and Genomics Lab (IDG) in the UB-CoEBLS, which is directly connected to the Basic Life Sciences Building (BLSB) of RPCI. The instrument will be incorporated into the existing multi-core structure providing shared resources to UB-CoEBLS and RPCI. These cores provide support for a broad spectrum of services, including DNA sequencing, microarrays, genotyping, proteomics, as well as informatics and statistical support. The IDG core currently offers 454-FLX Titanium sequencing as a service to UB-CoEBLS-RPCI. The 454-FLX technology is complementary to the GAIIx, but is not capable of the throughput and flexibility needed for the applications increasingly used by UB-CoEBLS-RPCI investigators. The need for a GAIIx shared resource is clearly supported by the 10 ongoing and planned CoEBLS-RPCI projects utilizing a GAIIx instrument at other institutions and the 17 faculty with funded projects included in this proposal. The GAIIx will be used for CHiP-Seq to interrogate genome-wide protein-nucleic acid interactions, small RNA profiling for gene regulation and expression studies, PCR amplicon sequencing, SNP genotyping and identification of mutations in candidate disease genes, finishing of bacterial genomes and comparative genomic resequencing to identify novel virulence factors. Addition of the GAIIx technology as a cost effective shared resource will provide NIH funded faculty at UB-CoEBLS-RPCI with access to this key technology which is crucial to strengthen and further our research pursuits across the prevention, clinical, translational and basic research missions of our institutions.